PMID- 19616866 OWN - NLM STAT- MEDLINE DCOM- 20100907 LR - 20181201 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 68 IP - 2 DP - 2010 May TI - Assessment of mean EGFR gene copy number is a highly reproducible method for evaluating FISH in histological and cytological cancer specimens. PG - 192-7 LID - 10.1016/j.lungcan.2009.06.019 [doi] AB - The aims of this study were first, to systematically assess the inter-observer reproducibility of mean Epidermal Growth Factor Receptor (EGFR) gene copy number (MCN) in histological and cytological specimens from lung and non-lung cancers, second to compare the performance of this quantitative approach to the current Colorado criteria for the assessment of fluorescence in situ hybridization (FISH) positivity and third to develop a model to convert cytology into histology MCN. EGFR FISH analysis was performed on 170 histological and 153 cytological specimens. The MCN and Colorado criteria were assessed by two independent observers and agreement evaluated using Bland-Altman plots and kappa values. Conversion of cytology into histology MCN was tested on two randomized subgroups of specimens. Applying the Colorado criteria, agreement between observers was moderate with histology (k=0.5) and excellent with cytology (k=0.94). Positivity in histology versus cytology led to fair agreement (k=0.33). MCN was significantly greater in cytology compared to histology (p<0.001) with excellent inter-observer agreement in both sample types (r=0.99 and 0.89, respectively). The average difference in MCN between observers was -0.003 (95%CI: -0.05 to 0.05) and 0.008 (95%CI: -0.09 to 0.11) for cytology and histology, respectively. A reliable conversion model with an R(2)-value of 0.91 in the validation subgroup (p<0.001) was obtained. The MCN is a reproducible scoring method for evaluating EGFR FISH in samples from lung and non-lung cancers. This quantitative scoring system may constitute an alternative to current methods of gene copy number assessment and will further help to optimize patient selection for targeted therapies. CI - Copyright 2009 Elsevier Ireland Ltd. All rights reserved. FAU - Zlobec, Inti AU - Zlobec I AD - Institute for Pathology, University of Basel, Schonbeinstrasse 40, Basel 4031, Switzerland. FAU - Raineri, Ines AU - Raineri I FAU - Schneider, Sandra AU - Schneider S FAU - Schoenegg, Rene AU - Schoenegg R FAU - Grilli, Bruno AU - Grilli B FAU - Herzog, Michelle AU - Herzog M FAU - Savic, Spasenija AU - Savic S FAU - Bubendorf, Lukas AU - Bubendorf L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090718 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adenocarcinoma/*diagnosis/epidemiology/genetics/pathology/physiopathology MH - Diagnosis, Differential MH - Disease Progression MH - ErbB Receptors/*genetics MH - Feasibility Studies MH - *Gene Dosage MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Lung Neoplasms/*diagnosis/epidemiology/genetics/pathology/physiopathology MH - Observer Variation MH - Predictive Value of Tests EDAT- 2009/07/21 09:00 MHDA- 2010/09/08 06:00 CRDT- 2009/07/21 09:00 PHST- 2009/05/15 00:00 [received] PHST- 2009/06/17 00:00 [revised] PHST- 2009/06/20 00:00 [accepted] PHST- 2009/07/21 09:00 [entrez] PHST- 2009/07/21 09:00 [pubmed] PHST- 2010/09/08 06:00 [medline] AID - S0169-5002(09)00374-2 [pii] AID - 10.1016/j.lungcan.2009.06.019 [doi] PST - ppublish SO - Lung Cancer. 2010 May;68(2):192-7. doi: 10.1016/j.lungcan.2009.06.019. Epub 2009 Jul 18.